Method for detection of cleavage product of soluble amyloid-b precursor protein 770b for diagnosis of diseases associated with accumulation of amyloid-b peptide

Abstract

The present invention provides a method of detecting soluble amyloid β precursor protein 770β derived from vascular endothelial cell, comprising the following steps: (1) a step of contacting a biological sample derived from a test subject suspected of having a disease accompanied by accumulation of amyloid β peptide with an antibody recognizing soluble amyloid β precursor protein β or an amyloid β precursor protein 770-specific antibody; and (2) a step of detecting soluble amyloid β precursor protein 770β in the complex formed in step (1).

1 . A method of detecting soluble amyloid β precursor protein 770β derived from vascular endothelial cell, comprising the following steps:
 (1) a step of contacting a biological sample derived from a test subject with an antibody recognizing soluble amyloid β precursor protein β or an amyloid β precursor protein 770-specific antibody; and 
 (2) a step of detecting soluble amyloid β precursor protein 770β in the complex formed in step (1). 
 
     
     
         2 . (canceled) 
     
     
         3 . The method according to  claim 1 , wherein the biological sample is blood, plasma or serum. 
     
     
         4 . The method according to  claim 1 , wherein the biological sample is cerebrospinal fluid. 
     
     
         5 . The method according to  claim 1 , wherein the biological sample is culture supernatant of vascular endothelial cell. 
     
     
         6 . The method according to  claim 1 , comprising, in addition to steps (1) and (2), detection of soluble amyloid β precursor protein 695β by the following steps:
 (3) a step of contacting a biological sample derived from the test subject suspected of having a disease accompanied by accumulation of amyloid β peptide, with an antibody recognizing soluble amyloid β precursor protein β or soluble amyloid β precursor protein 695β-specific antibody; and 
 (4) a step of detecting soluble amyloid β precursor protein 695β in the complex formed in step (3). 
 
     
     
         7 . The method according to  claim 6 , wherein, in step (3), one of the antibody recognizing soluble amyloid β precursor protein β and the amyloid β precursor protein 695-specific antibody is used, and
 step (4) comprises 
 (4a) a step of contacting soluble amyloid β precursor protein 695β in the complex formed in step (3), with the antibody recognizing soluble amyloid β precursor protein β or soluble amyloid β precursor protein 695β-specific antibody, which was not used in step (3); and 
 (4b) a step of detecting the complex formed in step (4a). 
 
     
     
         8 . The method according to  claim 6 , wherein the biological sample in step (1) is blood, plasma, serum, culture supernatant of vascular endothelial cell or cerebrospinal fluid, and the biological sample in step (3) is cerebrospinal fluid. 
     
     
         9 . The method according to  claim 1 , wherein the amyloid β precursor protein 770-specific antibody is an antibody recognizing OX2 domain. 
     
     
         10 . The method according to  claim 1 , wherein the test subject is suspected of having a disease accompanied by accumulation of amyloid β peptide. 
     
     
         11 . The method according to  claim 10 , wherein the disease is at least any one of cerebrovascular amyloid angiopathy, cerebrovascular dementia, cerebral infarction and Alzheimer's disease. 
     
     
         12 . The method according to  claim 1 , wherein the test subject is suspected of having Alzheimer's disease occurring in association with at least any one of cerebrovascular amyloid angiopathy, cerebrovascular dementia and cerebral infarction. 
     
     
         13 .- 17 . (canceled) 
     
     
         18 . A method of detecting soluble amyloid β precursor protein 770β derived from vascular endothelial cell, comprising the following steps:
 (1) a step of contacting a biological sample derived from a test subject with an antibody recognizing soluble amyloid β precursor protein β or an amyloid β precursor protein 770-specific antibody; 
 (2a) a step of contacting soluble amyloid β precursor protein 770β in the complex formed in step (1) with the antibody recognizing soluble amyloid β precursor protein β or amyloid β precursor protein 770-specific antibody, which was not used in step (1); and 
 (2b) a step of detecting the complex formed in step (2a). 
 
     
     
         19 . The method according to  claim 18 , wherein the biological sample is blood, plasma, serum, cerebrospinal fluid or culture supernatant of vascular endothelial cell. 
     
     
         20 . The method according to  claim 18 , comprising, in addition to steps (1), (2a) and (2b), detection of soluble amyloid β precursor protein 695β by the following steps:
 (3) a step of contacting a biological sample derived from the test subject suspected of having a disease accompanied by accumulation of amyloid β peptide, with an antibody recognizing soluble amyloid β precursor protein β or soluble amyloid β precursor protein 695β-specific antibody; 
 (4a) a step of contacting soluble amyloid β precursor protein 695β in the complex formed in step (3), with the antibody recognizing soluble amyloid β precursor protein β or soluble amyloid β precursor protein 695β-specific antibody, which was not used in step (3); and 
 (4b) a step of detecting the complex formed in step (4a). 
 
     
     
         21 . The method according to  claim 20 , wherein the biological sample in step (1) is blood, plasma, serum, culture supernatant of vascular endothelial cell or cerebrospinal fluid, and the biological sample in step (3) is cerebrospinal fluid. 
     
     
         22 . The method according to  claim 18 , wherein the amyloid β precursor protein 770-specific antibody is an antibody recognizing OX2 domain. 
     
     
         23 . The method according to  claim 18 , wherein the test subject is suspected of having a disease accompanied by accumulation of amyloid β peptide. 
     
     
         24 . The method according to  claim 23 , wherein the disease is at least any one of cerebrovascular amyloid angiopathy, cerebrovascular dementia, cerebral infarction and Alzheimer's disease. 
     
     
         25 . The method according to  claim 18 , wherein the test subject is suspected of having Alzheimer's disease occurring in association with at least any one of cerebrovascular amyloid angiopathy, cerebrovascular dementia and cerebral infarction.